Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis

Gabriele Ruffolo; Katiuscia Martinello; Angelo Labate; Pierangelo Cifelli; Sergio Fucile; Giancarlo di Gennaro; Andrea Quattrone; Vincenzo Esposito; Cristina Limatola; Felice Giangaspero; Eleonora Aronica; Eleonora Palma; Antonio Gambardella

doi:https://doi.org/10.1002/acn3.51150

Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis

Gabriele Ruffolo, Katiuscia Martinello, Angelo Labate, Pierangelo Cifelli, Sergio Fucile, Giancarlo di Gennaro, Andrea Quattrone, Vincenzo Esposito, Cristina Limatola, Felice Giangaspero, Eleonora Aronica, Eleonora Palma, Antonio Gambardella

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Abstract

We compared GABAergic function and neuronal excitability in the hippocampal tissue of seven sporadic MTLE patients with a patient carrying a SCN1A loss-of-function mutation. All had excellent outcome from anterior temporal lobectomy, and neuropathological study always showed characteristic hippocampal sclerosis (Hs). Compared to MTLE patients, there was a more severe impairment of GABAergic transmission, due to the lower GABAergic activity related to the NaV1.1 loss-of-function, in addition to the typical GABA-current rundown, a hallmark of sporadic MTLE. Our results give evidence that a pharmacological rescuing of the GABAergic dysfunction may represent a promising strategy for the treatment of these patients.

Original language	English
Pages (from-to)	1726-1731
Number of pages	6
Journal	Annals of clinical and translational neurology
Volume	7
Issue number	9
Early online date	2020
DOIs	https://doi.org/10.1002/acn3.51150
Publication status	Published - 1 Sept 2020

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Ruffolo, G., Martinello, K., Labate, A., Cifelli, P., Fucile, S., di Gennaro, G., Quattrone, A., Esposito, V., Limatola, C., Giangaspero, F., Aronica, E., Palma, E., & Gambardella, A. (2020). Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis. Annals of clinical and translational neurology, 7(9), 1726-1731. https://doi.org/10.1002/acn3.51150

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title = "Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis",

abstract = "We compared GABAergic function and neuronal excitability in the hippocampal tissue of seven sporadic MTLE patients with a patient carrying a SCN1A loss-of-function mutation. All had excellent outcome from anterior temporal lobectomy, and neuropathological study always showed characteristic hippocampal sclerosis (Hs). Compared to MTLE patients, there was a more severe impairment of GABAergic transmission, due to the lower GABAergic activity related to the NaV1.1 loss-of-function, in addition to the typical GABA-current rundown, a hallmark of sporadic MTLE. Our results give evidence that a pharmacological rescuing of the GABAergic dysfunction may represent a promising strategy for the treatment of these patients.",

author = "Gabriele Ruffolo and Katiuscia Martinello and Angelo Labate and Pierangelo Cifelli and Sergio Fucile and {di Gennaro}, Giancarlo and Andrea Quattrone and Vincenzo Esposito and Cristina Limatola and Felice Giangaspero and Eleonora Aronica and Eleonora Palma and Antonio Gambardella",

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Ruffolo, G, Martinello, K, Labate, A, Cifelli, P, Fucile, S, di Gennaro, G, Quattrone, A, Esposito, V, Limatola, C, Giangaspero, F, Aronica, E, Palma, E & Gambardella, A 2020, 'Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis', Annals of clinical and translational neurology, vol. 7, no. 9, pp. 1726-1731. https://doi.org/10.1002/acn3.51150

TY - JOUR

T1 - Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis

AU - Ruffolo, Gabriele

AU - Martinello, Katiuscia

AU - Labate, Angelo

AU - Cifelli, Pierangelo

AU - Fucile, Sergio

AU - di Gennaro, Giancarlo

AU - Quattrone, Andrea

AU - Esposito, Vincenzo

AU - Limatola, Cristina

AU - Giangaspero, Felice

AU - Aronica, Eleonora

AU - Palma, Eleonora

AU - Gambardella, Antonio

PY - 2020/9/1

Y1 - 2020/9/1

N2 - We compared GABAergic function and neuronal excitability in the hippocampal tissue of seven sporadic MTLE patients with a patient carrying a SCN1A loss-of-function mutation. All had excellent outcome from anterior temporal lobectomy, and neuropathological study always showed characteristic hippocampal sclerosis (Hs). Compared to MTLE patients, there was a more severe impairment of GABAergic transmission, due to the lower GABAergic activity related to the NaV1.1 loss-of-function, in addition to the typical GABA-current rundown, a hallmark of sporadic MTLE. Our results give evidence that a pharmacological rescuing of the GABAergic dysfunction may represent a promising strategy for the treatment of these patients.

AB - We compared GABAergic function and neuronal excitability in the hippocampal tissue of seven sporadic MTLE patients with a patient carrying a SCN1A loss-of-function mutation. All had excellent outcome from anterior temporal lobectomy, and neuropathological study always showed characteristic hippocampal sclerosis (Hs). Compared to MTLE patients, there was a more severe impairment of GABAergic transmission, due to the lower GABAergic activity related to the NaV1.1 loss-of-function, in addition to the typical GABA-current rundown, a hallmark of sporadic MTLE. Our results give evidence that a pharmacological rescuing of the GABAergic dysfunction may represent a promising strategy for the treatment of these patients.

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U2 - https://doi.org/10.1002/acn3.51150

DO - https://doi.org/10.1002/acn3.51150

M3 - Article

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SN - 2328-9503

VL - 7

SP - 1726

EP - 1731

JO - Annals of clinical and translational neurology

JF - Annals of clinical and translational neurology

IS - 9

ER -

Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis

Abstract

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